Analgesic prescribing trends in a national sample of older veterans with osteoarthritis: 2012-2017

Few investigations examine patterns of opioid and nonopioid analgesic prescribing and concurrent pain intensity ratings before and after institution of safer prescribing programs such as the October 2013 Veterans Health Administration system-wide Opioid Safety Initiative (OSI) implementation. We conducted a quasi-experimental pre–post observational study of all older U.S. veterans (≥50 years old) with osteoarthritis of the knee or hip. All associated outpatient analgesic prescriptions and outpatient pain intensity ratings from January 1, 2012 to December 31, 2016, were analyzed with segmented regression of interrupted time series. Standardized monthly rates for each analgesic class (total, opioid, nonsteroidal anti-inflammatory drug, acetaminophen, and other study analgesics) were analyzed with segmented negative binomial regression models with overall slope, step, and slope change. Similarly, segmented linear regression was used to analyze pain intensity ratings and percentage of those reporting pain. All models were additionally adjusted for age, sex, and race. Before OSI implementation, total analgesic prescriptions showed a steady rise, abruptly decreasing to a flat trajectory after OSI implementation. This trend was primarily due to a decrease in opioid prescribing after OSI. Total prescribing after OSI implementation was partially compensated by continuing increased prescribing of other study analgesics as well as a significant rise in acetaminophen prescriptions (post-OSI). No changes in nonsteroidal anti-inflammatory drug prescribing were seen. A small rise in the percentage of those reporting pain but not mean pain intensity ratings continued over the study period with no changes associated with OSI. Changes in analgesic prescribing trends were not paralleled by changes in reported pain intensity for older veterans with osteoarthritis

Optimizing Neutron Yield for Active Interrogation

Neutrons are commonly used for many applications, including active interrogation and cancer therapy. One critical aspect for active interrogation efficiency is neutron yield, which is more important for successful resolution than the energy spectrum. The typical approach for improving neutron yield entails producing more neutrons, which has motivated multiple studies using the interaction of increasingly more powerful tabletop lasers with plastic targets to generate protons or deuterons that are absorbed by another target to create neutrons [1]. Alternatively, one may use lenses to focus the neutrons to increase yield rather than simply generating more neutrons with more powerful lasers [2]. Assessing either approach requires a comprehensive model simulating neutron generation and transport to optimize the target material, system geometry, and neutron yield. A complete model from laser source to neutron generation is beyond the scope of the current study, so this project focuses on simulating the interaction of deuterons with typical target materials, such as lithium or beryllium. We use the neutron transport code Monte Carlo N-Particles (MCNP), which applies the Monte Carlo method to track particles [3]. The simulations accurately reflected experimental results from several groups [4]. Future analyses will assess improvements in neutron yield and directionality through strategically incorporating neutron lenses

Effects of Gangliosides on the Activity of the Plasma Membrane Ca2+-ATPase

Control of intracellular calcium concentrations ([Ca2+]i) is essential for neuronal function, and the plasma membrane Ca2+-ATPase (PMCA) is crucial for the maintenance of low [Ca2+]i. We previously reported on loss of PMCA activity in brain synaptic membranes during aging. Gangliosides are known to modulate Ca2+ homeostasis and signal transduction in neurons. In the present study, we observed age-related changes in the ganglioside composition of synaptic plasma membranes. This led us to hypothesize that alterations in ganglioside species might contribute to the age-associated loss of PMCA activity. To probe the relationship between changes in endogenous ganglioside content or composition and PMCA activity in membranes of cortical neurons, we induced depletion of gangliosides by treating neurons with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP). This caused a marked decrease in the activity of PMCA, which suggested a direct correlation between ganglioside content and PMCA activity. Neurons treated with neuraminidase exhibited an increase in GM1 content, a loss in poly-sialoganglioside content, and a decrease in PMCA activity that was greater than that produced by D-PDMP treatment. Thus, it appeared that poly-sialogangliosides had a stimulatory effect whereas mono-sialogangliosides had the opposite effect. Our observations add support to previous reports of PMCA regulation by gangliosides by demonstrating that manipulations of endogenous ganglioside content and species affect the activity of PMCA in neuronal membranes. Furthermore, our studies suggest that age-associated loss in PMCA activity may result in part from changes in the lipid environment of this Ca2+ transporter

A Search for Multi-Planet Systems Using the Hobby-Eberly Telescope

Extrasolar multiple-planet systems provide valuable opportunities for testing theories of planet formation and evolution. The architectures of the known multiple-planet systems demonstrate a fascinating level of diversity, which motivates the search for additional examples of such systems in order to better constrain their formation and dynamical histories. Here we describe a comprehensive investigation of 22 planetary systems in an effort to answer three questions: 1) Are there additional planets? 2) Where could additional planets reside in stable orbits? and 3) What limits can these observations place on such objects? We find no evidence for additional bodies in any of these systems; indeed, these new data do not support three previously announced planets (HD 20367b: Udry et al. 2003, HD 74156d: Bean et al. 2008, and 47 UMa c: Fischer et al. 2002). The dynamical simulations show that nearly all of the 22 systems have large regions in which additional planets could exist in stable orbits. The detection-limit computations indicate that this study is sensitive to close-in Neptune-mass planets for most of the systems targeted. We conclude with a discussion on the implications of these non-detections.Comment: Accepted to ApJS. Includes 39 pages of radial-velocity data table

A sub-horizon framework for probing the relationship between the cosmological matter distribution and metric perturbations

The relationship between the metric and nonrelativistic matter distribution depends on the theory of gravity and additional fields, providing a possible way of distinguishing competing theories. With the assumption that the geometry and kinematics of the homogeneous universe have been measured to sufficient accuracy, we present a procedure for understanding and testing the relationship between the cosmological matter distribution and metric perturbations (along with their respective evolution) using the ratio of the physical size of the perturbation to the size of the horizon as our small expansion parameter. We expand around Newtonian gravity on linear, subhorizon scales with coefficient functions in front of the expansion parameter. Our framework relies on an ansatz which ensures that (i) the Poisson equation is recovered on small scales (ii) the metric variables (and any additional fields) are generated and supported by the nonrelativistic matter overdensity. The scales for which our framework is intended are small enough so that cosmic variance does not significantly limit the accuracy of the measurements and large enough to avoid complications from nonlinear effects and baryon cooling. The coefficient functions provide a general framework for contrasting the consequences of Lambda CDM and its alternatives. We calculate the coefficient functions for general relativity with a cosmological constant and dark matter, GR with dark matter and quintessence, scalar-tensor theories, f(R) gravity and braneworld models. We identify a possibly unique signature of braneworld models. Constraining the coefficient functions provides a streamlined approach for testing gravity in a scale dependent manner. We briefly discuss the observations best suited for an application of our framework.Comment: Updated references and minor changes to match the published version in MNRA

Vegetation response to invasive Tamarix control in southwestern U.S. rivers: a collaborative study including 416 sites

Most studies assessing vegetation response following control of invasive Tamarix trees along southwestern U.S. rivers have been small in scale (e.g., river reach), or at a regional scale but with poor spatial-temporal replication, and most have not included testing the effects of a now widely used biological control. We monitored plant composition following Tamarix control along hydrologic, soil, and climatic gradients in 244 treated and 172 reference sites across six U.S. states. This represents the largest comprehensive assessment to date on the vegetation response to the four most common Tamarix control treatments. Biocontrol by a defoliating beetle (treatment 1) reduced the abundance of Tamarix less than active removal by mechanically using hand and chain-saws (2), heavy machinery (3) or burning (4). Tamarix abundance also decreased with lower temperatures, higher precipitation, and follow-up treatments for Tamarix resprouting. Native cover generally increased over time in active Tamarix removal sites, however, the increases observed were small and was not consistently increased by active revegetation. Overall, native cover was correlated to permanent stream flow, lower grazing pressure, lower soil salinity and temperatures, and higher precipitation. Species diversity also increased where Tamarix was removed. However, Tamarix treatments, especially those generating the highest disturbance (burning and heavy machinery), also often promoted secondary invasions of exotic forbs. The abundance of hydrophytic species was much lower in treated than in reference sites, suggesting that management of southwestern U.S. rivers has focused too much on weed control, overlooking restoration of fluvial processes that provide habitat for hydrophytic and floodplain vegetation. These results can help inform future management of Tamarix-infested rivers to restore hydrogeomorphic processes, increase native biodiversity and reduce abundance of noxious species

New invasive Nemertean species (Cephalothrix Simula) in England with high levels of tetrodotoxin and a microbiome linked to toxin metabolism

The marine nemertean Cephalothrix simula originates from the Pacific Ocean but in recent years has been discovered in northern Europe. The species has been associated with high levels of the marine neurotoxin Tetrodotoxin, traditionally associated with Pufferfish Poisoning. This study reports the first discovery of two organisms of C. simula in the UK, showing the geographical extent of this species is wider than originally described. Species identification was initially conducted morphologically, with confirmation by Cox 1 DNA sequencing. 16S gene sequencing enabled the taxonomic assignment of the microbiome, showing the prevalence of a large number of bacterial genera previously associated with TTX production including Alteromonas, Vibrio and Pseudomonas. LC-MS/MS analysis of the nemertean tissue revealed the presence of multiple analogues of TTX, dominated by the parent TTX, with a total toxin concentration quantified at 54 µg TTX per g of tissue. Pseudomonas luteola isolated from C. simula, together with Vibrio alginolyticus from the native nemertean Tubulanus annulatus, were cultured at low temperature and both found to contain TTX. Overall, this paper confirms the high toxicity of a newly discovered invasive nemertean species with links to toxin-producing marine bacteria and the potential risk to human safety. Further work is required to assess the geographical extent and toxicity range of C. simula along the UK coast in order to properly gauge the potential impacts on the environment and human safety